Discussion was minimal, given the agreement on a very high level of enthusiasm. It was noted that these are innovative experiments proposed by a pioneer in the field. The collaboration with Dr. Smith was felt to be an added strength. DESCRIPTION (Adapted from the applicant's abstract): The overall objective of this competitive renewal application is to determine the brainstem mechanisms responsible for respiratory and sympathetic rhythmic activities that are the basis for respiratory and circulatory functioning during various physiological conditions. One series of experiments are designed to characterize the functions of different brainstem respiratory neurons in generation of respiratory rhythm and pattern. They will ascertain time relations between different respiratory neurons and between these neurons and respiratory motor outputs (e.g., phrenic nerve), as influenced by perturbation of the respiratory pattern (e.g., vagal and superior laryngeal inputs). Phase-switching mechanisms will be studied in another series of experiments involving simultaneous recordings of brainstem neuronal activity and phrenic and laryngeal nerve activities in response to perturbations that change the pattern of respiration. These studies include intracellular recordings of membrane potentials immediately preceding inspiratory or expiratory off-switch. Connectivity between pairs of respiratory neurons will be studied using both time-domain and frequency-domain correlational techniques in both in vivo and in vitro preparations. The final project is an analysis of slow and fast rhythms in sympathetic nerve discharge. Slow rhythms include a respiratory-related and a non-respiratory related component. Fast rhythms are at 3 Hz and 10 Hz. The neuronal basis for respiratory modulation of sympathetic activity will be studied by recording from medullary "sympathetic-related" neurons during different respiratory conditions. Relationships between sympathetic activity, phrenic nerve activity, and individual neurons will be studied by using coherence, partial coherence, and bispectral techniques. One hypothesis to be tested is that slow sympathetic rhythms arise by modulation of the faster rhythms.